Serum‐Based Detection of Liver Pathology Using a Fluorogenic Alkaline Phosphatase Probe

Author:

Zhou Tijian1,Li Li2,Zhu Zhirong1,Chen Xiaoyan2,Wang Qi1,Zhu Wei‐Hong1ORCID

Affiliation:

1. Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials and Institute of Fine Chemicals Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel Prize Scientist Joint Research Center Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology 200237 Shanghai China

2. Department of Pathology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Abstract

AbstractDevelopment of “ultrahigh contrast” fluorogenic probes for trapping alkaline phosphatase (ALP) activities in human serum is highly desirable for clinical auxiliary diagnosis for hepatobiliary diseases. However, the intrinsic dilemma of incomplete ionization of intramolecular charge transfer (ICT)‐based ALP fluorophores and autofluorescence interference of serum result in low sensitivity and accuracy. Given that unique halogen effects could lead to a drastic decrease in the pKa value and a significant enhancement in the fluorescence quantum yield, herein we report an enzyme‐activatable near‐infrared probe based on a difluoro‐substituted dicyanomethylene‐4H‐chromenep for achieving fluorescent quantification of human serum ALP. Rational design strategy is demonstrated by altering the substituted halogen groups to well regulate the pKa for meeting the physiological precondition. Owing to the complete ionization at pH 7.4 with tremendous fluorescence enhancement, the difluoro‐substituted DCM‐2F‐HP manifests a linear relationship between the emission intensity and ALP concentration in both solution and serum samples. Along with measuring 77 human serum samples, the DCM‐2F‐HP based fluorescence method not only exhibits significant correlations with clinical colorimetry, but also distinguishes ALP patients from healthy volunteers, as well as assessing the progress of liver disease, thus providing a potential toolbox for quantitatively detecting ALP and warning the stage of hepatopathy.

Funder

National Key Research and Development Program of China

Publisher

Wiley

Subject

Organic Chemistry,Molecular Biology,Molecular Medicine,Biochemistry

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